Corticosteroids, particularly in the form of the ester derivative compounds, are used, inter alia, in the treatment of skin diseases in humans, such as eczema, infantile eczema, atopic dermatitis, dermatitis herpetiformis, contact dermatitis, seborrhoeic dermatitis, neurodermatitis, psoriasis and intertrigo. Formulations containing such active substances have conventionally been applied to the skin site in the form of alcoholic solutions, lotions or creams.
However, lotions and creams can be too viscous to permit efficient penetration of the active substance to the epidermis, and solutions have a tendency to evaporate before penetrating the epidermis. In addition, conventional cream bases can be irritating to the skin, particularly over the often long exposure that is required, and the fluidity of lotions often makes the physical application difficult to control. Moreover, it is necessary to rub such formulations into the target site to improve the penetration of the active substance into the epidermis, an action that itself can produce irritation.
There has therefore been a very real need in the treatment of skin disorders requiring treatment with corticosteroids for improved formulations which target the most effective corticosteroid to the skin site with improved delivery of active, substance with decreased inconvenience and irritation, and increased ease of use for the patient. One such improvement has been in the product sold under the name Olux® (clobetasol propionate) Foam 0.05%. Olux® Foam 0.05% contains clobetasol propionate in a thermolabile hydroethanolic foam vehicle pressurized by a hydrocarbon (propane/butane) propellant. This product is described and claimed in U.S. Pat. No. 6,126,920.
The product label, inter alia, instructs morning and evening applications that can be effected by inverting the pressurized container and dispensing a small amount of the hair mousse-like foam (up to a maximum of a golf-ball-size dollop or one and a half capfuls) into the cap of the can, onto a saucer or other cool surface, or to the lesion, taking care to avoid contact with the eyes. Dispensing directly onto hands is not recommended (unless the hands are the affected area), as the foam will begin to melt immediately upon contact with warm skin. Small amounts of the foam are suggested to be picked up with fingertips and gently massaged into affected area until the foam disappears.
U.S. Pat. No. 7,029,659 and U.S. Pat. No. 6,730,288 both to Abram that are titled “Mousse Composition” and U.S. Pat. No. 8,460,641 to Larm et al. describe aerosol foaming compositions for dermatological use. The Abram compositions are described as a mousse, whereas a Larm et al. composition is described as an oil in water microemulsion or sub-micron emulsion that can be dispensed “as an aerosol foam or mousse” (col. 16, lines 35-36). A composition of each patent is said to contain at least one occlusive agent such as one or both of petrolatum and mineral oil, one or more lipophilic surfactants, water, at least one hydrophilic surfactant, a non-surfactant water-soluble amphiphilic agent such as a diol or polyol, a pharmaceutically active ingredient that is poorly water-soluble such as betamethasone valerate or clobetasol propionate, and a propellant. A composition of the three patents can also contain an organic solvent.
Each of these patents is listed in the FDA “Orange Book” in conjunction with a product called “Olux-E®”. This product is to be indicated for the treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 12 years and older. The active ingredient is 0.05% clobetasol propionate. The instructions for use of Olux-E® indicate that the aerosol container be shaken, and inverted to dispense the foam into the palm of one's hand. The dispensed foam is then to be applied to the affected area in a thin layer and the foam gently rubbed into the affected area until it disappears into the skin.
The Olux® (clobetasol propionate) Foam 0.05% product is a particularly efficacious product, but is somewhat inconvenient and cumbersome to use because of the requirement for container inversion to dispense the foam and the related difficulties in dispensing the foam into the container cap, the stiffness of the dispensed foam that can require excessive rubbing and irritation on use, and the wastage involved in dispensing the foam into the product cap and scooping out the dispensed foam with the user's fingers to apply it to the affected area. The present invention provides improvements in these areas, while maintaining the desired pharmaceutical results.